Sympathetic neural discharge patterns, co-transmitters and neurovascular control

交感神经系统通过血管收缩状态的改变，对血压的时刻变化起着重要的调节作用。这个系统发出交感神经活动（SNA）的爆发，由多个神经元大致同时放电。本研究项目验证了SNA的放电模式通过多种神经递质的差异释放不同程度地影响血管舒缩控制的工作假设。主要目标是：1)量化在SNA综合爆发中存在的神经元动作电位的编码模式，它们的反射特异性和物种特异性。将使用小波去噪方法和其他基于matlab的算法来揭示和表征多单元神经记录中的单个动作电位。2)建立基于受体的不同影响骨骼肌血管树力学特性的机制。采用改进的Windkessel模型，测量了人类前臂和大鼠后肢骨骼肌在反射运动过程中的阻力、顺应性、粘弹性和惯性的集总参数及其基于受体的控制机制。3)量化生理上相关的SNA放电模式对血管舒缩力学的影响及其基于连接后受体的控制机制，强调压力反射与肌肉化学反射激活。我们将模拟SNA动作电位的模式，以复制不同大小、分组和间隔的SNA爆发。这些将被回放到麻醉的啮齿动物的股神经中，并测量对血管阻力和顺应性的基于受体的变化的影响。这些实验将提供新颖和创新的方法来研究交感神经元与血管沟通的方式，以施加短期和长期的血管控制。这些研究包括综合动物生理学，为科学发现和培养高素质人才提供了独特的机会。

The sympathetic nervous system is an important regulator of moment-by-moment changes in blood pressure through changes in vascular contractile state. This system emits bursts of sympathetic nerve activity (SNA) consisting of multiple neurons discharging at more-or-less the same time. This research program tests the working hypothesis that the discharge patterns of SNA variously impact vasomotor control through the differential release of multiple neurotransmitters. The major objectives are: 1) Quantify the coded patterns of neuronal action potentials present within integrated bursts of SNA, their reflex-specificity, and their species-specificity. Wavelet denoising methods and other Matlab-based algorithms will be used to expose and characterize individual action potentials in the multi-unit nerve recordings. 2) Establish the receptor-based mechanisms that differentially affect the mechanical properties of the vascular tree in skeletal muscle. Using a modified Windkessel model, the lumped parameters of resistance, compliance, viscoelasticity and inertia will be measured in the skeletal muscle of the human forearm and the rat hindlimb during reflexive manoeuvres along with their receptor-based mechanism of control. 3) Quantify the impact of physiologically relevant SNA discharge patterns on vasomotor mechanics and their post-junctional receptor-based mechanism of control, emphasizing baroreflex versus muscle chemoreflex activation. We will simulate patterns of SNA action potentials that replicate SNA bursts of varying sizes, groupings, and inter-burst spacing. These will be played back into the femoral nerve of an anesthetized rodent and the impact on receptor-based changes in vascular resistance and compliance will be measured. The experiments will provide novel and innovative approaches to examine the manner in which sympathetic neurons communicate with blood vessels to exert short-, and longer-term vascular control. These studies embrace integrative animal physiology and offer a unique opportunity for scientific discovery and for training of highly qualified personnel.